The BACTEC 460 TB System (Becton Dickinson Diagnostic Instrument Systems, Sparks, MD) is widely used to test susceptibility of clinical isolates of Mycobacterium tuberculosis. This system provides more rapid susceptibility results than other available methodologies, and its use is recommended for the earliest possible detection by nonmolecular methods of multidrug-resistant M. tuberculosis (MDR-TB) isolates. Some preliminary studies from our laboratory suggest that some of the organism inoculum recommendations provided by the manufacturer may not in fact be optimal and may require repetition of the test to obtain interpretable results. We are currently engaged in a systematic evaluation of different inoculum sizes with this system, using both sensitive and resistant isolates, because our data suggest that MDR- TB isolates may have growth characteristics different from sensitive isolates.